Targeted protein aggregation as a new antiviral drug development platform

Viruses are infectious pathogenic entities that use host elements to multiply and lead to a wide range of human diseases. Although antiviral drugs have previously been developed, for the last ten years very few new therapeutics have reached the market. This lack of progress is alarming since new viruses emerge and the well-known ones develop resistance rapidly, rendering the existing drugs ineffective. The intrinsic nature of viruses is challenging the current antiviral drug development pipelines, which lack pace and efficiency, and new platforms are needed to design antiviral agents with an increased potency and decreased toxicity. Here, we study the use of targeted protein aggregation for the design of new antiviral agents. Protein aggregation is the mechanism in which proteins clump together and as a result lose their original function. Targeted aggregation aims to induce the specific aggregation of a certain protein by exposing it to a short peptide whose sequence is based on the aggregation core of the targeted protein. Viral protein aggregation will lead to a loss-of-function and inactivation of viral replication. Almost all viral proteins contain these aggregation cores and thus can be targeted by this technology. We aim to exploit the use of the targeted aggregation technology as a platform to inactivate important pathogenic viruses, including Zika virus, dengue virus and Hepatitis C virus.